PMID- 10469356
OWN - NLM
STAT- MEDLINE
DCOM- 19991021
LR  - 20081121
IS  - 0085-2538 (Print)
IS  - 0085-2538 (Linking)
VI  - 56
IP  - 3
DP  - 1999 Sep
TI  - c-Rel and p65 trans-activate the monocyte chemoattractant protein-1 gene in 
      interleukin-1 stimulated mesangial cells.
PG  - 873-82
AB  - BACKGROUND: The chemokine monocyte chemoattractant protein-1 (MCP-1) is secreted 
      by human glomerular mesangial cells in response to interleukin-1 (IL-1) and has a 
      central role in amplifying the inflammatory response during glomerulonephritis. 
      However, the mechanism by which IL-1 regulates its transcription is not 
      understood. Specific members of the nuclear factor kappaB/rel (NF-kappaB) 
      proteins may regulate MCP-1 expression in a stimulus- and tissue-specific manner. 
      METHODS: Electrophoretic mobility shift assays and Western blot analysis 
      characterized the members of the NF-kappaB family that bound the two NF-kappaB 
      sites of the MCP-1 enhancer (A1 and A2) in vitro. Trans-activation of the MCP-1 
      gene was investigated by transfer of the MCP-1 enhancer DNA to mesangial cells. 
      RESULTS: Primary human mesangial cells contained in addition to p50 (NF-kappaB1) 
      and p65 (Rel A) NF-kappaB proteins, the oncoprotein c-rel, and Rel B, but not p52 
      (NF-kappaB2). IL-1 induced c-rel to form a complex with p65, which bound the 
      MCP-1 A2 site but not the A1 or IL-6 NF-kappaB sites in vitro. IL-1 up-regulated 
      transfected MCP-1 enhancer activity. Cotransfer of the MCP-1 enhancer together 
      with individual members of the NF-kappaB family showed that the heterodimer 
      c-relp65 or (p65)2 can selectively trans-activate the MCP-1 gene via its A1 and 
      A2 sites in mesangial cells. CONCLUSIONS: This study demonstrates for the first 
      time that the c-rel oncoprotein can enhance MCP-1 transcription in mesangial 
      cells and suggests that it may have an important role in amplifying gene 
      expression in the inflamed glomerulus.
FAU - Stylianou, E
AU  - Stylianou E
AD  - Division of Renal and Inflammatory Disease, School of Medical and Surgical 
      Sciences, University of Nottingham, England, United Kingdom. 
      Eleni.Stylianou@Nottingham.ac.uk
FAU - Nie, M
AU  - Nie M
FAU - Ueda, A
AU  - Ueda A
FAU - Zhao, L
AU  - Zhao L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Kidney Int
JT  - Kidney international
JID - 0323470
RN  - 0 (Chemokine CCL2)
RN  - 0 (Interleukin-1)
RN  - 0 (Interleukin-6)
RN  - 0 (NF-kappa B)
RN  - 0 (Oligonucleotide Probes)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Proto-Oncogene Proteins c-rel)
RN  - 0 (RELB protein, human)
RN  - 0 (Relb protein, rat)
RN  - 0 (Transcription Factors)
RN  - 147337-75-5 (Transcription Factor RelB)
RN  - EC 6.- (Ligases)
RN  - EC 6.- (guanosine 3',5'-polyphosphate synthetases)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Binding Sites/genetics
MH  - Cells, Cultured
MH  - Chemokine CCL2/*genetics
MH  - Enhancer Elements, Genetic
MH  - Glomerular Mesangium/cytology/*drug effects/*metabolism
MH  - Humans
MH  - Interleukin-1/*pharmacology
MH  - Interleukin-6/genetics
MH  - Ligases/*metabolism
MH  - NF-kappa B/metabolism
MH  - Oligonucleotide Probes/genetics
MH  - Promoter Regions, Genetic
MH  - Proto-Oncogene Proteins/*metabolism
MH  - Proto-Oncogene Proteins c-rel
MH  - Rats
MH  - Transcription Factor RelB
MH  - Transcription Factors/metabolism
MH  - Transcriptional Activation
MH  - Transfection
EDAT- 1999/09/01 00:00
MHDA- 1999/09/01 00:01
CRDT- 1999/09/01 00:00
PHST- 1999/09/01 00:00 [pubmed]
PHST- 1999/09/01 00:01 [medline]
PHST- 1999/09/01 00:00 [entrez]
AID - S0085-2538(15)46366-5 [pii]
AID - 10.1046/j.1523-1755.1999.00640.x [doi]
PST - ppublish
SO  - Kidney Int. 1999 Sep;56(3):873-82. doi: 10.1046/j.1523-1755.1999.00640.x.